Increased expression of annexin I is associated with drug-resistance in nasopharyngeal carcinoma and other solid tumors

Adjuvant chemotherapy alongside radiotherapy is one of the effective therapies in nasopharyngeal carcinoma (NPC) treatment. However, the appearance of drug resistance is a major obstacle for anti-cancer chemotherapy and often causes failure of the chemotherapy. In this study, a drug-resistant gene annexin I (ANX-I) was identified by comparing differentially expressed proteins between a cisplatin (CDDP)-resistant NPC cell line CNE2-CDDP and parental CNE2 cells using 2-DE. When ANX-I was transfected into CNE2 cells, the CDDP resistance of CNE2 cells was dramatically increased. The drug-resistant ability of ANX-I was demonstrated by both in vitro and in vivo assays. The association of ANX-I expression with clinical features was also investigated. Increased expression of ANX-I was significantly associated with disease relapse in NPC (p<0.05). In breast and gastric cancer, increased expression of ANX-I was significantly associated with drug resistance (p<0.001) and poor prognosis (p<0.001), respectively. Taken together, our findings suggest that ANX-I plays an important role in drug resistance.     

Quantitative proteomic analysis of a paired human liver healthy versus carcinoma cell lines with the same genetic background to identify potential hepatocellular carcinoma markers

To comprehensively measure global changes in protein expression associated with human hepatocellular carcinoma (HCC), comparative proteomic analysis of two cell lines derived from the healthy and carcinoma tissue of a same donor respectively was conducted using quantitative amino acid-coded mass tagging /stable isotope labeling with amino acids in cell culture-based LC-MS/MS approach. Among a total of 501 proteins precisely quantified, the expressions of 128 proteins were significantly altered including 70 proteins up-regulated and 58 down-regulated in HCC cells. According to their previously characterized functions, the differentially expressed proteins were found associated with nine functional categories including glycolysis, stress response, cell communication, cell cycle, apoptosis/death, etc. For example, multiple enzymes involving glycolysis pathway were found differentially regulated in HCC cells, illustrating the critical participation of glycolysis in the HCC transformation. The accuracy of certain differentially expressed proteins identified through the amino acid-coded mass tagging-based quantification was validated in the paired cell lines, and later their pathological correlations were examined in multiple clinical pairs of normal versus tumor tissues from HCC specimen by using a variety of biological approaches including Western blotting and in situ immunoassays. These consistencies suggested that multiple proteins such as HSP27, annexin V, glyceraldehyde-3-phosphate dehydrogenase, nucleolin and elongation factor Tu could be the biomarkers candidates for diagnosis of HCC.     

Comparison of membrane-associated proteins in human cholangiocarcinoma and hepatocellular carcinoma cell lines

Cholangiocarcinoma (CCA) and hepatocellular carcinoma (HCC) occur with relatively high incidence in Thailand. Cell line models, originating from Thai patients, are available for both diseases, including the human bile duct epithelial carcinoma cell line (HuCCA-1) and the HCC cell line HCC-S102. Here, we have prepared subproteomes enriched in membrane proteins or in cytosolic proteins from the HuCCA-1 and the HCC-S102 cell lines. Study of differential protein expression by 2-DE and LC/MS/MS showed 195 proteins expressed in the two cell lines, including both membrane-associated and cytosolic proteins. Eighteen proteins were found in both membrane and cytosolic fractions of HuCCA-1, but not in HCC-S102, while nine proteins were found in both membrane and cytosolic fractions of HCC-S102, but not in HuCCA-1. Ten membrane proteins were found in HuCCA-1 but not in HCC-S102, including integrin alpha-6 precursor, ezrin, hippocalcin-like protein 1, mitogen-activated protein kinase kinase kinase 2 (MAPK/ERK kinase kinase 2), and calgizzarin. Proteins showing increased expression in the membrane fraction of HuCCA-1 were mainly cytoskeletal proteins (40.9%), while proteins showing increased expression in the membrane fraction of HCC-S102 were mainly metabolic proteins (39.4%). The subproteomic approach used here facilitates detection of potential biomarkers undetected by regular proteomic methods.     

Discovery of stage-related proteins in esophageal squamous cell carcinoma using proteomic analysis

Esophageal squamous cell carcinoma (ESCC) is the major subtype of esophageal cancers in China, and characterized with high morbidity and mortality. So far, the diagnosis of ESCC is mainly dependent on the alterations in esophageal histology, but most cases of ESCC with low stage do not display visible histological abnormalities. Therefore, a deep understanding of the mechanism of ESCC progression and seeking stage-specific molecules might improve the diagnosis and therapy for ESCC. In this study, we used proteomics to analyze ESCC tissues with classification by TNM stage, and determined the proteomic features correlated with ESCC progression (from stages I to III). Proteins that exhibited significantly different expression patterns between ESCC and corresponding normal esophageal tissues were identified using MS. The identified proteins with differentiated expression mainly fell into three protein categories (i.e. cytoskeleton system-associated proteins, metabolism enzymes, and heat shock proteins). In addition, real-time PCR highlighted some molecules that were associated with tumor stages at the mRNA level, such as enolase 1, chromosome 1 ORF 10, elastase inhibitor, α B crystalline, stress-induced phosphoprotein 1, and squamous cell carcinoma antigen 1. Altogether, these data provided further information on ESCC progression and potential drug targets for ESCC clinical therapy.     

Computing survival functions of the sum of two independent Markov processes: an application to bladder carcinoma treatment

The study of the sum of two independent phase-type (PH)-distributed variables, each of them being associated with a Markovian process with one absorbing state, is considered in this paper. The distribution function of the variable sum is computed, obtaining a new PH-distributed function of higher order. As the order increases in the new function, the exponential function of a block upper triangular matrix is calculated in terms of its respective blocks to reduce the dimension of the problem. The obtained results are applied to bladder carcinoma data.     

负载食管癌抗原肽的脐血树突状细胞诱导杀瘤活性研究

为探讨负载酸洗脱食管癌抗原肽的脐血树突状细胞(DCs)对细胞毒T细胞(CTL)杀伤活性的影响,本研究采用密度梯度离心法分离脐血中的单个核细胞(CBMNC),在重组人粒巨噬细胞集落刺激因子(rhGM-CSF)、重组白介素(rhIL-4)及重组肿瘤坏死因子(rhTNF-a)的配伍作用下,以酸洗脱食管癌抗原肽负载获得分化成熟DCs,利用CytoTox 96试剂盒检测其对特异性CTL的诱导和体外杀伤效应的影响。结果:负载食管癌抗原肽的脐血DCs诱导的CTL对酸洗前食管癌细胞株T.Tn的杀伤率达(78.5±9.5)%,显著高于酸洗后组和各对照组(P<0.05),而对无关肿瘤细胞株Hep2无显著杀伤作用(P<0.05)。结论:负载食管癌抗原肽的脐血DCs体外可诱导CTL产生特异性杀伤效应。本研究为食管癌的免疫治疗提供了新的有效途经。     

LHRH-PE40与宫颈癌组织结合特性的研究

目的观察LHRH-PE40对各种病理型宫颈癌组织的结合能力,为其临床应用提供理论依据。方法采用免疫荧光法检测LHRH-PE40与正常宫颈组织及宫颈癌组织的结合能力。结果宫颈结缔组织、鳞状上皮的荧光结合率为0%。宫颈癌组织荧光结合率为74%,弱阳性及阴性表达病例中,高分化鳞状细胞癌占67%,中低分化鳞状细胞癌占15%,两者差异有显著意义(P<0.05)。中强阳性表达病例中,高分化鳞状细胞癌仅占37%,中低分化鳞状细胞癌占86%,两者差异有显著意义(P<0.05)。5例强阳性表达病例均为高分化腺癌。结论高分化鳞状细胞癌与LHRH-PE40结合能力最弱,子宫颈腺癌与LHRH-PE40结合能力最强。     

同步辐射X荧光研究肝细胞癌组织和癌旁组织微粒体内的金属蛋白分布

用差速离心法提取肝细胞癌组织和癌旁组织的微粒体组分,用等电聚焦(IEF)分离微粒体内的蛋白质,用同步辐射X荧光(SRXRF)测定各蛋白条带内微量元素的含量得到金属蛋白分布信息.结果在肝细胞癌组织以及癌旁组织的微粒体中共检出7个含锰条带、8个含铁条带、6个含铜条带和8个含锌条带.癌组织和癌旁组织微粒体的相应蛋白条带内的金属含量相近,但在癌组织的等电点(pI)为5.9的含铁条带中铁含量仅为癌旁组织相应条带的40%,在pI为93的条带中铜、锌的含量分别是癌旁组织的2倍和35倍.研究结果表明,癌组织和癌旁组织的金属蛋白分布模式明显不同,金属蛋白分布的区别可能与肝组织的癌变相关.     

The Effect of Nano-apatite on the Expression of Telomerase Gene of Human Hepatocellular Carcinoma Cells

1Introduction Theactivityoftelomeraseinmostmalignanttumor cellscanbedetected,butislowinthenormalsomatic cells[1],sothedetectionofactivityoftelomerasemaybe comeabreakthroughinearlydiagnosingandcuringtu mor.Theperfectbio compatibilityofnano apatitearein ter…